Patient Identification of Diagnostic Safety Blindspots and Participation in "Good Catches" Through Shared Visit Notes.

Policy Points Patients and families can identify clinically relevant errors, including "blindspots"-safety hazards that are difficult for clinicians or organizations to see. Health information transparency, including patient access to electronic visit notes, now federally mandated in the US and the subject of policy debate worldwide, creates a new opportunity to engage patients in diagnostic safety. However, not all patients access notes. Patient identification of blindspots in their notes underscores the need to systematically and equitably engage willing patients in safety, promote patient "good catches," and establish routine systems for patient feedback to help avoid preventable diagnostic errors and delays. CONTEXT: Policy shifts toward health information transparency provide a new opportunity for patients to contribute to diagnostic safety. We investigated whether sharing clinical notes with patients can support identification of "diagnostic safety blindspots"-potentially consequential breakdowns in the diagnostic process that may be difficult for clinical staff to observe. METHOD: We used mixed methods to analyze patient-reported ambulatory documentation errors among 22,889 patients at three US health care centers who read ≥ 1 visit note(s). We identified blindspots by tailoring a previously established taxonomy. We used multiple regression analysis to identify factors associated with blindspot identification. FINDINGS: 774 patients reported a total of 962 blindspots in 4 categories: (1) diagnostic misalignments (n = 421, 43.8%), including inaccurate symptoms or histories and failures or delay in diagnosis; (2) errors of omission (38.1%) including missed main concerns or next steps, and failure to listen to patients; (3) problems occurring outside visits (14.3%) such as tests, referrals, or appointment access; and (4) multiple low-level problems (3.7%) cascading into diagnostic breakdowns. Many patients acted on the blindspots they identified, resulting in "good catches" that may prevent potential negative consequences. Older, female, sicker, unemployed or disabled patients, or those who work in health care were more likely to identify a blindspot. Individuals reporting less formal education; those self-identifying as Black, Asian, other, or multiple races; and participants who deferred decision-making to providers were less likely to report a blindspot. CONCLUSION: Patients who read notes have unique insight about potential errors in their medical records that could impact diagnostic reasoning but may not be known to clinicians-underscoring a critical role for patients in diagnostic safety and organizational learning. From a policy standpoint, organizations should encourage patient review of visit notes, build systems to track patient-reported blindspots, and promote equity in note access and blindspot reporting.

The Safer Culture Framework: An Application to Healthcare Based on a Multi-Industry Review of Safety Culture Literature.

BACKGROUND: Errors and preventable harm to patients remain regrettably common and expensive in healthcare. Improvement requires transforming the culture of the healthcare industry to put a greater emphasis on safety. Safety culture involves holding collective attitudes, values, and behaviors that prioritize safety. The Safer Culture framework, previously established through a narrative review of literature in multiple industries, provides a consensus on what impacts safety culture, how it manifests in behavior, and how it influences safety-related outcomes. METHODS: Through a theoretical review, we validate, refine, and provide nuance to this framework for the development of safety culture in healthcare contexts. To accomplish this, we conceptually map existing dimensions pulled through the literature onto our Safer Culture framework. RESULTS: A total of 360 articles were reviewed. We present specific elements for each dimension in our framework and apply the dimension to healthcare contexts. CONCLUSION: We provide an evidence-based and comprehensive framework that can be used by patient safety leaders and researchers to guide the evaluation of safety culture and develop interventions to foster patient safety culture and improve patient safety outcomes.

Safety Culture: An Integration of Existing Models and a Framework for Understanding Its Development.

OBJECTIVE: This study reviews theoretical models of organizational safety culture to uncover key factors in safety culture development. BACKGROUND: Research supports the important role of safety culture in organizations, but theoretical progress has been stunted by a disjointed literature base. It is currently unclear how different elements of an organizational system function to influence safety culture, limiting the practical utility of important research findings. METHOD: We reviewed existing models of safety culture and categorized model dimensions by the proposed function they serve in safety culture development. We advance a framework grounded in theory on organizational culture, social identity, and social learning to facilitate convergence toward a unified approach to studying and supporting safety culture. RESULTS: Safety culture is a relatively stable social construct, gradually shaped over time by multilevel influences. We identify seven enabling factors that create conditions allowing employees to adopt safety culture values, assumptions, and norms; and four behaviors used to enact them. The consequences of these enacting behaviors provide feedback that may reinforce or revise held values, assumptions, and norms. CONCLUSION: This framework synthesizes information across fragmented conceptualizations to clearly depict the dynamic nature of safety culture and specific drivers of its development. We suggest that safety culture development may depend on employee learning from behavioral outcomes, conducive enabling factors, and consistency over time. APPLICATION: This framework guides efforts to understand and develop safety culture in practice and lends researchers a foundation for advancing theory on the complex, dynamic processes involved in safety culture development.

Towards 20,20-difluorinated bryostatin: synthesis and biological evaluation of C17,C27-fragments.

Bryostatins with modified C17-C27 fragments have not been widely studied. The synthesis of 20,20-difluorinated analogues was therefore investigated. Such substitution would inhibit dehydration involving the C19-hydroxyl group and stabilise the ring-closed hemiacetal tautomers. Following preliminary studies, allyldifluorination was used to prepare difluorinated alkenols. Oxidation followed by stereoselective Wittig reactions of the resulting α,α-difluorinated ketones gave (E)-α,ß-unsaturated esters that were taken through to complete syntheses of 2-hydroxytetrahydropyrans corresponding to C17-C27 fragments of 20,20-difluorinated bryostatin. These compounds showed modest binding to protein kinase Cα isozyme. Attempts were also undertaken to synthesise macrocyclic 20,20-difluorinated analogues. During preliminary studies, allyldifluorination was carried out using a 2-alkyl-3-bromo-1,1-difluoropropene.

Safety climate, safety climate strength, and length of stay in the NICU.

BACKGROUND: Safety climate is an important marker of patient safety attitudes within health care units, but the significance of intra-unit variation of safety climate perceptions (safety climate strength) is poorly understood. This study sought to examine the standard safety climate measure (percent positive response (PPR)) and safety climate strength in relation to length of stay (LOS) of very low birth weight (VLBW) infants within California neonatal intensive care units (NICUs). METHODS: Observational study of safety climate from 2073 health care providers in 44 NICUs. Consistent perceptions among a NICU's respondents, i.e., safety climate strength, was determined via intra-unit standard deviation of safety climate scores. The relation between safety climate PPR, safety climate strength, and LOS among VLBW (< 1500 g) infants was evaluated using log-linear regression. Secondary outcomes were infections, chronic lung disease, and mortality. RESULTS: NICUs had safety climate PPRs of 66 ± 12%, intra-unit standard deviations 11 (strongest) to 23 (weakest), and median LOS 60 days. NICUs with stronger climates had LOS 4 days shorter than those with weaker climates. In interaction modeling, NICUs with weak climates and low PPR had the longest LOS, NICUs with strong climates and low PPR had the shortest LOS, and NICUs with high PPR (both strong and weak) had intermediate LOS. Stronger climates were associated with lower odds of infections, but not with other secondary outcomes. CONCLUSIONS: Safety climate strength is independently associated with LOS and moderates the association between PPR and LOS among VLBW infants. Strength and PPR together provided better prediction than PPR alone, capturing variance in outcomes missed by PPR. Evaluations of NICU safety climate consider both positivity (PPR) and consistency of responses (strength) across individuals.

Development of a framework to describe patient and family harm from disrespect and promote improvements in quality and safety: a scoping review.

PURPOSE: Patients and families may experience 'non-physical' harm from interactions with the healthcare system, including emotional, psychological, socio-behavioral or financial harm, some of which may be related to experiences of disrespect. We sought to use the current literature to develop a practical, improvement-oriented framework to recognize, describe and help prevent such events. DATA SOURCES: Searches were performed in PubMed, Embase, PsychINFO, CINAHL, Health Business Elite and ProQuest Dissertations & Theses: Global: Health & Medicine, from their inception through July 2017. STUDY SELECTION: Two authors reviewed titles, abstracts, full texts, references and cited-by lists to identify articles describing approaches to understanding patient/family experiences of disrespect. DATA EXTRACTION: Findings were evaluated using integrative review methodology. RESULTS OF DATA SYNTHESIS: Three-thousand eight hundred and eighty two abstracts were reviewed. Twenty three articles were identified. Components of experiences of disrespect included: (1) numerous care processes; (2) a wide range of healthcare professional and organizational behaviors; (3) contributing factors, including patient- and professional-related factors, the environment of work and care, leadership, policies, processes and culture; (4) important consequences of disrespect, including behavioral changes and health impacts on patients and families, negative effects on professionals' subsequent interactions, and patient attrition from organizations and (5) factors both intrinsic and extrinsic to patients that can modify the consequences of disrespect. CONCLUSION: A generalizable framework for understanding disrespect experienced by patients/families in healthcare may help organizations better prevent non-physical harms. Future work should prospectively test and refine the framework we described so as to facilitate its integration into organizations' existing operational systems.

An Ethnography of Parents' Perceptions of Patient Safety in the Neonatal Intensive Care Unit.

BACKGROUND: Parents of neonates are integral components of patient safety in the neonatal intensive care unit (NICU), yet their views are often not considered. By understanding how parents perceive patient safety in the NICU, clinicians can identify appropriate parent-centered strategies to involve them in promoting safe care for their infants. PURPOSE: To determine how parents of neonates conceptualize patient safety in the NICU. METHODS: We conducted qualitative interviews with 22 English-speaking parents of neonates from the NICU and observations of various parent interactions within the NICU over several months. Data were analyzed using thematic content analysis. Findings were critically reviewed through peer debriefing. FINDINGS: Parents perceived safe care through their observations of clinicians being present, intentional, and respectful when adhering to safety practices, interacting with their infant, and communicating with parents in the NICU. They described partnering with clinicians to promote safe care for their infants and factors impacting that partnership. We cultivated a conceptual model highlighting how parent-clinician partnerships can be a core element to promoting NICU patient safety. IMPLICATIONS FOR PRACTICE: Parents' observations of clinician behavior affect their perceptions of safe care for their infants. Assessing what parents observe can be essential to building a partnership of trust between clinicians and parents and promoting safer care in the NICU. IMPLICATIONS FOR RESEARCH: Uncertainty remains about how to measure parent perceptions of safe care, the level at which the clinician-parent partnership affects patient safety, and whether parents' presence and involvement with their infants in the NICU improve patient safety.

Synthesis of macrocyclic precursors of the vioprolides.

The vioprolides are novel depsipeptides that have not been synthesized. However, they have been identified as important targets for synthesis because of their novel biological activities and challenging chemical structures. Following early work on the synthesis of a modified tetrapeptide that contained both the (E)-dehydrobutyrine and thiazoline components of vioprolide D, problems were encountered in taking an (E)-dehydrobutyrine containing intermediate further into the synthesis. A second approach to vioprolides and analogues was therefore investigated in which (E)- and (Z)-dehydrobutyrines were to be introduced by selenoxide elimination very late in the synthesis. A convergent approach to advanced macrocyclic precursors of the vioprolides was then completed using a modified hexapeptide and a dipeptidyl glycerate. In this work, it was necessary to protect the 2-hydroxyl group of the glycerate as its acetate and not as its 2,2,2-trichloroethoxycarbonate. Preliminary studies were carried out on the introduction of the required dehydrobutyrine and thiazoline components into advanced intermediates.

A Multi-Stakeholder Consensus-Driven Research Agenda for Better Understanding and Supporting the Emotional Impact of Harmful Events on Patients and Families.

BACKGROUND: The nature and consequences of patient and family emotional harm stemming from preventable medical error, such as losing a loved one or surviving serious medical injury, is poorly understood. Patients and families, clinicians, social scientists, lawyers, and foundation/policy leaders were brought together to establish research priorities for this issue. METHODS: A one-day conference of diverse stakeholder groups to establish a consensus-driven research agenda focused on (1) priorities for research on the short-term and long-term emotional impact of harmful events on patients and families, (2) barriers and enablers to conducting such research, and (3) actionable steps toward better supporting harmed patients and families now. RESULTS: Stakeholders discussed patient and family experiences after serious harmful events, including profound isolation, psychological distress, damaging aspects of medical culture, health care aversion, and negative effects on communities. Stakeholder groups reached consensus, defining four research priorities: (1) Establish conceptual framework and patient-centered taxonomy of harm and healing; (2) Describe epidemiology of emotional harm; (3) Determine how to make emotional harm and long-term impacts visible to health care organizations and society at large; and (4) Develop and implement best practices for emotional support of patients and families. The group also created a strategy for overcoming research barriers and actionable "Do Now" approaches to improve the patient and family experience while research is ongoing. CONCLUSION: Emotional and other long-term impacts of harmful events can have profound consequences for patients and families. Stakeholders designed a path forward to inform approaches that better support harmed patients and families, with both immediately actionable and longer-term research strategies.

Syntheses of C17-C27 fragments of 20-deoxybryostatins for assembly using Julia and metathesis reactions.

Two approaches to the synthesis of compounds corresponding to the C17-C27 fragment of the 20-deoxybryostatins are described. The first approach is based on the palladium(0) catalysed coupling of tin enolates, generated in situ from enol acetates using tributyltin methoxide, with vinylic bromides. The vinylic bromides were prepared using the Sharpless asymmetric dihydroxylation to introduce the hydroxyl groups corresponding to those at C25 and C26 in the bryostatins. Following several steps to introduce alkynyl ester functionality, the stereoselective addition of a tributyltin cuprate followed by tributyltin-bromine exchange gave the required vinylic bromides. The palladium(0) catalysed couplings worked very well for enol esters containing thioether substituents and gave products with retention of the position and geometry of the trisubstituted double bond derived from the vinylic bromide. These were taken through to compounds corresponding to fully developed C17-C27 fragments ready for assembly of the 16,17-double-bond of bryostatins by Julia reactions. This chemistry was also applied to prepare intermediates suitable for incorporation into bryostatins by ring-closing metathesis but, in this case, the coupling reaction gave mixtures of products including both the required ßγ-unsaturated ketone and a conjugated diene formed by a competing Heck reaction. To avoid this problem, a second approach to compounds suitable for incorporation into a metathesis-based assembly of 20-deoxybryostatins was developed. In this organotin-free synthesis, the key step was the conjugate addition of an organic cuprate generated from allylmagnesium bromide to an alkynoate that gave the required (Z)-trisubstituted alkene with excellent stereoselectivity. This was converted into metathesis precursors in a few steps.

Some limitations of an approach to the assembly of bryostatins by ring-closing metathesis.

Preliminary studies into the use of ring-closing metathesis (RCM) in a convergent approach for the total synthesis of bryostatins are described. An ester that would have provided an advanced intermediate for a synthesis of a 20-deoxybryostatin by a RCM was prepared from an unsaturated acid and alcohol corresponding to the C1-C16 and C17-C27 fragments. However, studies of the formation of the C16-C17 double-bond by RCM were not successful and complex mixtures of products were obtained. To provide an insight into factors that may be involved in hindering RCM in this system, a slightly simplified C1-C16 acid and modified C17-C25 alcohols were prepared and their use for the synthesis of analogues of bryostatins was investigated. Although only low yields were obtained, it appeared that macrolides analogous to the bryostatins can be prepared by RCM, using the Grubbs II catalyst, if the precursors lack the two methyl groups at C18. RCM was not observed, however, for substrates in which these methyl groups were present.

Synthetic approaches to the C11-C27 fragments of bryostatins.

The modified Julia reaction and acyl carbanion chemistry, especially reactions of 2-lithiated dithianes, have been investigated for the synthesis of intermediates that are the synthetic equivalents of the C11-C27 fragments of bryostatins. The modified Julia reaction using 2-benzothiazolylsulfones was found to be more useful for the formation of the C16-C17 double-bond than the classical Julia reaction using phenylsulfones, and bulky sulfones gave very good (E)-stereoselectivity. The alkylation of a dithiane monoxide that corresponded to a C19-acyl carbanion using (E)-1-bromobut-2-ene was efficient but the use of a more complex allylic bromide corresponding to the C20-C27 fragment of the bryostatins was unsuccessful, possibly due to competing elimination reactions. This meant that the use of C19 dithianes for the synthesis of 20-deoxybryostatins would have to involve the stepwise assembly of the C20-C27 fragment from simpler precursors. However, lithiated C19 dithianes gave good yields of adducts with aldehydes and conditions were developed for the stereoselective conversion of the major adducts into methoxyacetals that corresponded to the C17-C27 fragment of 20-oxygenated bryostatins. A convergent synthesis of the C11-C27 fragment of a 20-deoxybryostatin was subsequently achieved using a 2-benzothiazolylsulfone corresponding to the intact C17-C27 fragment.

Total synthesis of 7-des-O-pivaloyl-7-O-benzylbryostatin 10.

The first total synthesis of a derivative of a 20-deoxybryostatin, namely 7-des-O-pivaloyl-7-O-benzylbryostatin 10 is described. Preliminary studies demonstrated that the modified Julia reactions of 2-benzothiazolylsulfones corresponding to the C17-C27 fragment with aldehydes corresponding to the C1-C16 fragment, provided an efficient and stereoselective assembly of advanced intermediates with the (E)-16,17-double-bond. The synthesis of the C1-C16 fragment was then modified so that the C1 acid was present as its allyl ester before the Julia coupling. A more efficient synthesis of the C17-C27 sulfone was developed in which a key step was the bismuth mediated coupling of an allylic bromide with an aldehyde in the presence of an acrylate moiety in the allylic bromide. A scalable synthesis of an advanced macrolide was completed using the modified Julia reaction followed by selective deprotection and macrolactonisation. The final stages of the synthesis required selective hydroxyl deprotection and the introduction of the sensitive C19-C21 unsaturated keto-ester functionality. Unexpected selectivities were observed during studies of the hydroxyl group deprotections. In particular, cleavage of tri-isopropylsilyl ethers of the exocyclic primary allylic alcohols was observed in the presence of the triethylsilyl ether of the secondary alcohol at C19. Model studies helped in the design of the methods used to introduce the C19-C21 keto-ester functionality and led to the completion of a total synthesis of a close analogue of bryostatin 10 in which a benzyloxy group rather than the pivaloyloxy group was present at C7.

Teamwork in the NICU Setting and Its Association with Health Care-Associated Infections in Very Low-Birth-Weight Infants.

Background and Objective Teamwork may affect clinical care in the neonatal intensive care unit (NICU) setting. The objective of this study was to assess teamwork climate across NICUs and to test scale-level and item-level associations with health care-associated infection (HAI) rates in very low-birth-weight (VLBW) infants. Methods Cross-sectional study of the association between HAI rates, defined as any bacterial or fungal infection during the birth hospitalization, among 6,663 VLBW infants cared for in 44 NICUs between 2010 and 2012. NICU HAI rates were correlated with teamwork climate ratings obtained in 2011 from 2,073 of 3,294 eligible NICU health professionals (response rate 63%). The relation between HAI rates and NICU teamwork climate was assessed using logistic regression models including NICU as a random effect. Results Across NICUs, 36 to 100% (mean 66%) of respondents reported good teamwork. HAI rates were significantly and independently associated with teamwork climate (odds ratio, 0.82; 95% confidence interval, 0.73-0.92, p = 0.005), such that the odds of an infant contracting a HAI decreased by 18% with each 10% rise in NICU respondents reporting good teamwork. Conclusion Improving teamwork may be an important element in infection control efforts.

Accuracy of the Safer Dx Instrument to Identify Diagnostic Errors in Primary Care.

IMPORTANCE: Diagnostic errors are common and harmful, but difficult to define and measure. Measurement of diagnostic errors often depends on retrospective medical record reviews, frequently resulting in reviewer disagreement. OBJECTIVES: We aimed to test the accuracy of an instrument to help detect presence or absence of diagnostic error through record reviews. DESIGN: We gathered questions from several previously used instruments for diagnostic error measurement, then developed and refined our instrument. We tested the accuracy of the instrument against a sample of patient records (n = 389), with and without previously identified diagnostic errors (n = 129 and n = 260, respectively). RESULTS: The final version of our instrument (titled Safer Dx Instrument) consisted of 11 questions assessing diagnostic processes in the patient-provider encounter and a main outcome question to determine diagnostic error. In comparison with the previous sample, the instrument yielded an overall accuracy of 84 %, sensitivity of 71 %, specificity of 90 %, negative predictive value of 86 %, and positive predictive value of 78 %. All 11 items correlated significantly with the instrument's error outcome question (all p values ≤ 0.01). Using factor analysis, the 11 questions clustered into two domains with high internal consistency (initial diagnostic assessment, and performance and interpretation of diagnostic tests) and a patient factor domain with low internal consistency (Cronbach's alpha coefficients 0.93, 0.92, and 0.38, respectively). CONCLUSIONS: The Safer Dx Instrument helps quantify the likelihood of diagnostic error in primary care visits, achieving a high degree of accuracy for measuring their presence or absence. This instrument could be useful to identify high-risk cases for further study and quality improvement.

The synthesis of a series of adenosine A3 receptor agonists.

A series of 1'-(6-aminopurin-9-yl)-1'-deoxy-N-methyl-ß-d-ribofuranuronamides that were characterised by 2-dialkylamino-7-methyloxazolo[4,5-b]pyridin-5-ylmethyl substituents on N6 of interest for screening as selective adenosine A3 receptor agonists, have been synthesised. This work involved the synthesis of 2-dialkylamino-5-aminomethyl-7-methyloxazolo[4,5-b]pyridines and analogues that were coupled with the known 1'-(6-chloropurin-9-yl)-1'-deoxy-N-methyl-ß-d-ribofuranuronamide. The oxazolo[4,5-b]pyridines were synthesized by regioselective functionalisation of 2,4-dimethylpyridine N-oxides. The regioselectivities of these reactions were found to depend upon the nature of the heterocycle with 2-dimethylamino-5,7-dimethyloxazolo[4,5-b]pyridine-N-oxide undergoing regioselective functionalisation at the 7-methyl group on reaction with trifluoroacetic anhydride in contrast to the reaction of 4,6-dimethyl-3-hydroxypyridine-N-oxide with acetic anhydride that resulted in functionalisation of the 6-methyl group. To optimise selectivity for the A3 receptor, 5-aminomethyl-7-bromo-2-dimethylamino-4-[(3-methylisoxazol-5-yl)methoxy]benzo[d]oxazole was synthesised and coupled with the 1'-(6-chloropurin-9-yl)-1'-deoxy-N-methyl-ß-d-ribofuranuronamide. The products were active as selective adenosine A3 agonists.

The evolution of a stereoselective synthesis of the C1-C16 fragment of bryostatins.

The development of a synthesis of the C1-C16 fragment of bryostatins in which the key step is a stereoselective oxy-Michael reaction used to assemble the cis-2,6-disubstituted tetrahydropyran with the exocyclic alkene already installed, is described. Following early work using Stille reactions to prepare precursors for oxy-Michael reactions, a more efficient route was devised based on a ketophosphonate-aldehyde condensation to prepare the key dienone. Synthesis of the aldehyde required for the ketophosphonate condensation involved the highly stereoselective addition of a diorganocuprate derived from allylmagnesium bromide and copper(i) iodide to the methyl 5-hydroxyhex-2-ynoate prepared by ring-opening of a protected glycidol using lithiated methyl propiolate. Ester reduction, selective alcohol protection and oxidative cleavage of the terminal double bond gave the required aldehyde. The ketophosphonate was prepared in 13 steps from (R)-pantolactone using a synthesis based on a chelation controlled aldol condensation and an anti-selective reduction of a 3-hydroxyketone. Following the ketophosphonate-aldehyde reaction, selective deprotection followed by treatment with base effected the oxy-Michael reaction that gave the cis-2,6-disubstituted tetrahydropyran via thermodynamic control. Subsequent functional group manipulation led to the synthesis of a hydroxy ester that corresponded to the C1-C16 fragment of the bryostatins in 23 steps from (R)-pantolactone. The synthesis was repeated using slightly different protecting groups for a study of a ring-closing metathesis approach to the bryostatins.

Stereoselective synthesis of oxazolidinonyl-fused piperidines of interest as selective muscarinic (M1) receptor agonists: a novel M1 allosteric modulator.

Syntheses of (1RS,2SR,6SR)-2-alkoxymethyl-, 2-hetaryl-, and 2-(hetarylmethyl)-7-arylmethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones, of interest as potential muscarinic M1 receptor agonists, are described. A key step in the synthesis of (1RS,2SR,6SR)-7-benzyl-6-cyclobutyl-2-methoxymethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-one, was the addition of isopropenylmagnesium bromide to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal. This gave the 4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-isopropenyloxazolidinone with the 5-isopropenyl and 4-tert-butyldimethylsilyloxymethyl groups cis-disposed about the five-membered ring by chelation controlled addition and in situ cyclisation. This reaction was useful for a range of organometallic reagents. The hydroboration-oxidation of (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-(1-methoxyprop-2-en-2-yl)-1,3-oxazolidin-2-one gave (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-[(SR)-1-hydroxy-3-methoxyprop-2-yl]-1,3-oxazolidin-2-one stereoselectively. 4,7-Diaza-9-oxabicyclo[4.3.0]nonan-8-ones with substituents at C2 that could facilitate C2 deprotonation were unstable with respect to oxazolidinone ring-opening and this restricted both the synthetic approach and choice of 2-heteroaryl substituent. The bicyclic system with a 2-furyl substituent at C2 was therefore identified as an important target. The addition of 1-lithio-1-(2-furyl)ethene to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal gave (4SR,5RS)-4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-[1-(2-furyl)ethenyl]-1,3-oxazolidinone after chelation controlled addition and in situ cyclisation. Following oxazolidinone N-benzylation, hydroboration at 35 °C, since hydroboration at 0 °C was unexpectedly selective for the undesired isomer, followed by oxidation gave a mixture of side-chain epimeric alcohols that were separated after SEM-protection and selective desilylation. Conversion of the neopentylic alcohols into the corresponding primary amines by reductive amination, was followed by N-nosylation, removal of the SEM-groups and cyclisation using a Mitsunobu reaction. Denosylation then gave the 2-furyloxazolidinonyl-fused piperidines, the (1RS,2SR,6SR)-epimer showing an allosteric agonistic effect on M1 receptors. Further studies resulted in the synthesis of other 2-substituted 4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones and an analogous tetrahydropyran.

Development and Validation of Electronic Health Record-based Triggers to Detect Delays in Follow-up of Abnormal Lung Imaging Findings.

Purpose To develop an electronic health record (EHR)-based trigger algorithm to identify delays in follow-up of patients with imaging results that are suggestive of lung cancer and to validate this trigger on retrospective data. Materials and Methods The local institutional review board approved the study. A "trigger" algorithm was developed to automate the detection of delays in diagnostic evaluation of chest computed tomographic (CT) images and conventional radiographs that were electronically flagged by reviewing radiologists as being "suspicious for malignancy." The trigger algorithm was developed through literature review and expert input. It included patients who were alive and 40-70 years old, and it excluded instances in which appropriate timely follow-up (defined as occurring within 30 days) was detected (eg, pulmonary visit) or when follow-up was unnecessary (eg, in patients with a terminal illness). The algorithm was iteratively applied to a retrospective test cohort in an EHR data warehouse at a large Veterans Affairs facility, and manual record reviews were used to validate each individual criterion. The final algorithm aimed at detecting an absence of timely follow-up was retrospectively applied to an independent validation cohort to determine the positive predictive value (PPV). Trigger performance, time to follow-up, reasons for lack of follow-up, and cancer outcomes were analyzed and reported by using descriptive statistics. Results The trigger algorithm was retrospectively applied to the records of 89 168 patients seen between January 1, 2009, and December 31, 2009. Of 538 records with an imaging report that was flagged as suspicious for malignancy, 131 were identified by the trigger as being high risk for delayed diagnostic evaluation. Manual chart reviews confirmed a true absence of follow-up in 75 cases (trigger PPV of 57.3% for detecting evaluation delays), of which four received a diagnosis of primary lung cancer within the subsequent 2 years. Conclusion EHR-based triggers can be used to identify patients with suspicious imaging findings in whom follow-up diagnostic evaluation was delayed. (©) RSNA, 2015.

Surgical resident education in patient safety: where can we improve?

BACKGROUND: Effective communication and patient safety practices are paramount in health care. Surgical residents play an integral role in the perioperative team, yet their perceptions of patient safety remain unclear. We hypothesized that surgical residents perceive the perioperative environment as more unsafe than their faculty and operating room staff despite completing a required safety curriculum. MATERIALS AND METHODS: Surgeons, anesthesiologists, and perioperative nurses in a large academic children's hospital participated in multifaceted, physician-led workshops aimed at enhancing communication and safety culture over a 3-y period. All general surgery residents from the same academic center completed a hospital-based online safety curriculum only. All groups subsequently completed the psychometrically validated safety attitudes questionnaire to evaluate three domains: safety culture, teamwork, and speaking up. Results reflect the percent of respondents who slightly or strongly agreed. Chi-square analysis was performed. RESULTS: Sixty-three of 84 perioperative personnel (75%) and 48 of 52 surgical residents (92%) completed the safety attitudes questionnaire. A higher percentage of perioperative personnel perceived a safer environment than the surgical residents in all three domains, which was significantly higher for safety culture (68% versus 46%, P = 0.03). When stratified into two groups, junior residents (postgraduate years 1-2) and senior residents (postgraduate years 3-5) had lower scores for all three domains, but the differences were not statistically significant. CONCLUSIONS: Surgical residents' perceptions of perioperative safety remain suboptimal. With an enhanced safety curriculum, perioperative staff demonstrated higher perceptions of safety compared with residents who participated in an online-only curriculum. Optimal surgical education on patient safety remains unknown but should require a dedicated, systematic approach.